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Efficacy of sustained delivery of GC-1 from a Nanofluidic system in a spontaneously obese non-human primate: a case study

  • Carly S. Filgueira
  • Giacomo Bruno
  • Zachary W. Smith
  • Corrine Ying Xuan Chua
  • Andrea Ballerini
  • Marco Folci
  • April L. Gilbert
  • Priya Jain
  • Jagannadha K. Sastry
  • Pramod N. Nehete
  • Kathryn A. Shelton
  • Lori R. Hill
  • Areeba Ali
  • Keith A. Youker
  • Alessandro Grattoni
Article

Abstract

With nearly 40% of U.S. adults obese, and childhood and adolescent rates rising, obesity and associated comorbidities are serious public health concerns with massive societal costs. Often, lifestyle interventions do not offer sufficient weight loss to improve health, requiring surgery and medications as adjunct management strategies. Here, we present a 4-month case study in which the sustained, low-dose, and constant administration of the thyroid receptor β selective agonist GC-1 (sobetirome) from a novel nanochannel membrane implant was assessed in an obese, pre-diabetic rhesus macaque. Dramatic loss of white adipose tissue in the abdomen from 36 to 18% was observed via magnetic resonance imaging in conjunction with normalized serum insulin and glycemia, with no signs of cardiotoxicity shown. The non-human primate study highlights sustained low-dose delivery of GC-1 from our minimally invasive subcutaneous implant as a valuable approach to induce weight loss and manage obesity and comorbidities, including type 2 diabetes.

Keywords

GC-1 Sobetirome Thyroid hormone mimetics Sustained release Non-human primate 

Notes

Acknowledgements

The authors would like to acknowledge Drs. Kevin Phillips, Jean Lin, Paul Webb, Eugenia Nicolov, and Omaima Sabek for early discussions and project developments, Carlos Favela and Dr. Kemi Cui from the advanced cellular and tissue microscopy core, Dr. Andreana Rivera, Sandra Steptoe, and Dr. Yuelan Ren from the research pathology core. We also thank Dr. Greg Wilkerson, Luke Segura, Elizabeth Lindemann, and Debra Larsen from the Michale E. Keeling Center for Comparative Medicine and Research at MD Anderson Cancer Center, Dr. Yongying Jiang from the Pharmaceutical Science Facility, Institute of Applied Cancer Science, UT MD Anderson Cancer Center, and Dr. Jingfei Ma, Lindsay Wilson, and Michelle Underwood from MD Anderson Cancer Center. Membranes were provided by NanoMedical Systems, Inc. This work was supported by funds from Houston Methodist Research Institute (AG).

Author contributions

C.S.F. and A.G. designed the experiments. G.B. created the device schematics and performed the MRI analysis. C.S.F. and Z.W.S. performed the thyroid, pancreas, and liver imaging and analysis. A.A. and K.A.Y. performed the heart imaging and analysis. C.S.F., G.B., C.Y.X.C., A.B., M.F., and A.G. participated in drafting and/or revising of the manuscript. Primarily responsible for a particular specialized role (i) primate medicine: J.S., P.N.N., K.A.S., and L.R.H., (ii) blood processing: A.L.G., (iii) assisting with implantation: C.Y.X.C. and P.J.

Compliance with ethical standards

Competing interest

A.G. discloses a financial interest in NanoMedical Systems, Inc. All other authors declare no conflict of interest.

Supplementary material

10544_2018_296_MOESM1_ESM.docx (484 kb)
Figure S1 (DOCX 484 kb)
10544_2018_296_MOESM2_ESM.docx (128 kb)
Figure S2 (DOCX 127 kb)

References

  1. Advia Centaur Assay Manual T3 111634 Rev. L, 2008Google Scholar
  2. Advia Centaur Assay Manual T4 111619 Rev. L, 2008Google Scholar
  3. S. Ayers, P. Webb, J. Endocrinol. Diabetes Obes. 2, 1042 (2014)Google Scholar
  4. S.A. Bauer, T.P. Arndt, K.E. Leslie, D.L. Pearl, P.V. Turner, Comp. Med. 61, 514 (2011)Google Scholar
  5. J.D. Baxter, P. Webb, G. Grover, T.S. Scanlan, Trends Endocrinol. Metab. TEM 15, 154 (2004)CrossRefGoogle Scholar
  6. P.E. Belchetz, G. Gredley, R.L. Himsworth, J. Endocrinol. 76, 427 (1978)CrossRefGoogle Scholar
  7. “Belviq,” can be found under https://www.drugs.com/belviq.html, 2017
  8. E. Bonora, Int. J. Obes. Relat. Metab. Disord. 24(Suppl 2), S32 (2000)CrossRefGoogle Scholar
  9. Y. Chen, S. Qin, Y. Ding, L. Wei, J. Zhang, H. Li, H. Bu, Y. Lu, J. Cheng, Xenotransplantation 16, 496 (2009)CrossRefGoogle Scholar
  10. T. Deng, C.J. Lyon, S. Bergin, M.A. Caligiuri, W.A. Hsueh, Annu. Rev. Pathol. Mech. Dis. 11, 421 (2016)CrossRefGoogle Scholar
  11. C.L. Donohoe, S.L. Doyle, J.V. Reynolds, Diabetol. Metab. Syndr. 3, 12 (2011)CrossRefGoogle Scholar
  12. S. Ferrati, D. Fine, J. You, E. De Rosa, L. Hudson, E. Zabre, S. Hosali, L. Zhang, C. Hickman, S. Sunder Bansal, A.M. Cordero-Reyes, T. Geninatti, J. Sih, R. Goodall, G. Palapattu, M. Kloc, R.M. Ghobrial, M. Ferrari, A. Grattoni, J. Control. Release 172, 1011 (2013)CrossRefGoogle Scholar
  13. C.S. Filgueira, E. Nicolov, R.L. Hood, A. Ballerini, J. Garcia-Huidobro, J.Z. Lin, D. Fraga, P. Webb, O.M. Sabek, A.O. Gaber, K.J. Phillips, A. Grattoni, Int. J. Obes. 40, 1776 (2016)CrossRefGoogle Scholar
  14. C.S. Filgueira, A. Ballerini, E. Nicolov, C.Y.X. Chua, P. Jain, Z.W. Smith, A.L. Gilbert, F. Scaglione, A. Grattoni, N. Nanotechnol, Biol. Med. 13, 1739 (2017).  https://doi.org/10.1016/j.nano.2017.02.012. Google Scholar
  15. U.S. Food and Drug Administration, “Medications Target Long-Term Weight Control,” can be found under http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm312380.htm, 2015.
  16. F.R.S. Freitas, A.S. Moriscot, V. Jorgetti, A.G. Soares, M. Passarelli, T.S. Scanlan, G.A. Brent, A.C. Bianco, C.H.A. Gouveia, Am. J. Physiol. - Endocrinol. Metab. 285, E1135 (2003)CrossRefGoogle Scholar
  17. L.-E. García-Pérez, M. Álvarez, T. Dilla, V. Gil-Guillén, D. Orozco-Beltrán, Diabetes Ther. 4, 175 (2013)CrossRefGoogle Scholar
  18. A. Gonçalves, C.C. Tolentino, F.R. de Souza, J.C.d.C. Huss, K.d.L. Zinato, L.T.P. Lopes, R. Furlanetto Júnior, F.d.A.R. Neves, Arch. Endocrinol. Metab. 59, 141 (2015)CrossRefGoogle Scholar
  19. G.J. Grover, K. Mellström, L. Ye, J. Malm, Y.-L. Li, L.-G. Bladh, P.G. Sleph, M.A. Smith, R. George, B. Vennström, K. Mookhtiar, R. Horvath, J. Speelman, D. Egan, J.D. Baxter, Proc. Natl. Acad. Sci. U. S. A. 100, 10067 (2003)CrossRefGoogle Scholar
  20. G.J. Grover, D.M. Egan, P.G. Sleph, B.C. Beehler, G. Chiellini, N.-H. Nguyen, J.D. Baxter, T.S. Scanlan, Endocrinology 145, 1656 (2004)CrossRefGoogle Scholar
  21. A. Guilherme, J.V. Virbasius, V. Puri, M.P. Czech, Nat. Rev. Mol. Cell Biol. 9, 367 (2008)CrossRefGoogle Scholar
  22. A.J. Haertel, J.A. Stern, J.R. Reader, A. Spinner, J.A. Roberts, K.L. Christe, Comp. Med. 66, 333 (2016)Google Scholar
  23. H.J. Harwood Jr., P. Listrani, J.D. Wagner, J Diabetes Sci Technol 6, 503 (2012)CrossRefGoogle Scholar
  24. R. Hubrecht, J. Kirkwood, Universities Federation for Animal Welfare, Eds., The UFAW Handbook on the Care and Management of Laboratory and Other Research Animals, Wiley-Blackwell, Chichester, 2010Google Scholar
  25. K.L. Jen, B.C. Hansen, B.L. Metzger, Int. J. Obes. 9, 213 (1985)Google Scholar
  26. K.L. Johansen, J. Ren. Nutr. 23, 207 (2013)CrossRefGoogle Scholar
  27. A.A. Joharapurkar, V.V. Dhote, M.R. Jain, J. Med. Chem. 55, 5649 (2012)CrossRefGoogle Scholar
  28. D.A. Kanhai, L.J. Kappelle, Y. van der Graaf, C.S.P.M. Uiterwaal, F.L.J. Visseren, SMART Study Group, Int. J. Obes 2005(36), 695 (2012)CrossRefGoogle Scholar
  29. S. Karmali, B. Brar, X. Shi, A.M. Sharma, C. de Gara, D.W. Birch, Obes. Surg. 23, 1922 (2013)CrossRefGoogle Scholar
  30. A. Kim, K. Miller, J. Jo, G. Kilimnik, P. Wojcik, M. Hara, Islets 1, 129 (2009)CrossRefGoogle Scholar
  31. A. Krosnick, Prim. Care 15, 423 (1988)Google Scholar
  32. J.Z. Lin, A.J. Martagón, S.L. Cimini, D.D. Gonzalez, D.W. Tinkey, A. Biter, J.D. Baxter, P. Webb, J.-Å. Gustafsson, S.M. Hartig, K.J. Phillips, Cell Rep. 13, 1528 (2015)CrossRefGoogle Scholar
  33. Mayo Foundation for Medical Education and Research, “Common weight-loss drugs,” can be found under http://www.mayoclinic.org/healthy-lifestyle/weight-loss/in-depth/weight-loss-drugs/art-20044832?pg=2, n.d.
  34. J.I. Mechanick, A. Youdim, D.B. Jones, W. Timothy Garvey, D.L. Hurley, M. Molly, L.J. McMahon, R. Heinberg, T.D. Kushner, S. Adams, J.B. Shikora, S.B. Dixon, Surg. Obes. Relat. Dis. 9, 159 (2013)CrossRefGoogle Scholar
  35. E. Missov, C. Calzolari, B. Pau, Circulation 96, 2953 (1997)CrossRefGoogle Scholar
  36. A. Natalicchio, N. Marrano, G. Biondi, R. Spagnuolo, R. Labarbuta, I. Porreca, A. Cignarelli, M. Bugliani, P. Marchetti, S. Perrini, L. Laviola, F. Giorgino, Diabetes 2017, db170002Google Scholar
  37. Y. Okauchi, H. Iwahashi, K. Okita, T. Funahashi, K. Kishida, M. Noguchi, T. Ohira, T. Nakamura, A. Imagawa, I. Shimomura, J. Diabetes, Investig. 4, 454 (2013)Google Scholar
  38. C.M. Orrego, N. Nasir, G.H. Oliveira, J.H. Flores-Arredondo, A.M. Cordero-Reyes, M. Loebe, K.A. Youker, G. Torre-Amione, Congest. Heart Fail. Greenwich Conn 17, 140 (2011)CrossRefGoogle Scholar
  39. T.S. Scanlan, Heart Fail. Rev. 15, 177 (2010)CrossRefGoogle Scholar
  40. T.S. Scanlan, Safety and Pharmacodynamic Study of Sobetirome in X-Linked Adrenoleukodystrophy (X-ALD) (US, Oregon, 2013)Google Scholar
  41. Scanlan, T. S., Hartley, M., Placzek, A., Righi, M., Use of Sobetirome in the Treatment of X-Linked Adrenolenoleukodystrophy, n.d.Google Scholar
  42. A. Shoemaker, Sci. Transl. Med. 2017, 9, eaao2263Google Scholar
  43. T. Shoemaker, T. Kono, C. Mariash, C. Evans-Molina, Endocr. Pract. 18, 954 (2012)CrossRefGoogle Scholar
  44. J. Sih, S.S. Bansal, S. Filippini, S. Filipini, S. Ferrati, K. Raghuwansi, E. Zabre, E. Nicolov, D. Fine, M. Ferrari, G. Palapattu, A. Grattoni, Anal. Bioanal. Chem. 405, 1547 (2013)CrossRefGoogle Scholar
  45. L. Summers, K.J. Clingerman, X. Yang, J. Am. Assoc. Lab. Anim. Sci. JAALAS 51, 88 (2012)Google Scholar
  46. I. Tancevski, E. Demetz, P. Eller, Recent Patents Cardiovasc. Drug Discov. 6, 16 (2011)CrossRefGoogle Scholar
  47. S.U. Trost, E. Swanson, B. Gloss, D.B. Wang-Iverson, H. Zhang, T. Volodarsky, G.J. Grover, J.D. Baxter, G. Chiellini, T.S. Scanlan, W.H. Dillmann, Endocrinology 141, 3057 (2000)CrossRefGoogle Scholar
  48. Miriam E. Tucker, “FDA Approves Novel Implanted Device for Treating Obesity,” can be found under http://www.medscape.com/viewarticle/838176, 2015.
  49. C. P. Vega, C. M. Apovian, can be found under http://www.medscape.com/viewarticle/875655, n.d.
  50. P. Venditti, G. Chiellini, A. Bari, L. Di Stefano, R. Zucchi, A. Columbano, T.S. Scanlan, S. Di Meo, J. Exp. Biol. 212, 986 (2009)CrossRefGoogle Scholar
  51. J.D. Wagner, K. Kavanagh, G.M. Ward, B.J. Auerbach, H.J. Harwood, J.R. Kaplan, ILAR J. 47, 259 (2006)CrossRefGoogle Scholar
  52. A. Warner, J. Mittag, Adipocyte 3, 221 (2014)CrossRefGoogle Scholar
  53. D. Wescott, J. Hennan, D. Pavlock, J. Dipiero, D. Bounous, Clin. Chem. 58, A50 (2012)Google Scholar
  54. J.P.H. Wilding, Int. J. Clin. Pract. 68, 682 (2014)CrossRefGoogle Scholar
  55. S. Wolfensohn, in UFAW Handb. Care Manag. Lab. Res. Anim. Eight Ed., n.d.Google Scholar
  56. A.H. Wu, Y.J. Feng, J.H. Contois, S. Pervaiz, Ann. Clin. Lab. Sci. 26, 291 (1996)Google Scholar
  57. V. Xanthakis, M.G. Larson, K.C. Wollert, J. Aragam, S. Cheng, J. Ho, E. Coglianese, D. Levy, W.S. Colucci, G. Michael Felker, E.J. Benjamin, J.L. Januzzi, T.J. Wang, R.S. Vasan, J. Am. Heart Assoc. 2, e000399 (2013)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Carly S. Filgueira
    • 1
    • 2
  • Giacomo Bruno
    • 1
    • 3
  • Zachary W. Smith
    • 1
  • Corrine Ying Xuan Chua
    • 1
  • Andrea Ballerini
    • 1
  • Marco Folci
    • 1
  • April L. Gilbert
    • 1
  • Priya Jain
    • 1
  • Jagannadha K. Sastry
    • 4
  • Pramod N. Nehete
    • 5
  • Kathryn A. Shelton
    • 5
  • Lori R. Hill
    • 6
  • Areeba Ali
    • 7
  • Keith A. Youker
    • 7
  • Alessandro Grattoni
    • 1
    • 8
    • 9
  1. 1.Department of NanomedicineHouston Methodist Research InstituteHoustonUSA
  2. 2.Department of Cardiovascular SurgeryHouston Methodist HospitalHoustonUSA
  3. 3.Electronic and Communication DepartmentPolitecnico de TorinoTorinoItaly
  4. 4.Department of ImmunologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  5. 5.Department of Veterinary SciencesThe University of Texas M. D. Anderson Cancer CenterBastropUSA
  6. 6.Department of Veterinary Medicine and SurgeryThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  7. 7.Methodist DeBakey Heart & Vascular CenterHouston Methodist HospitalHoustonUSA
  8. 8.Department of SurgeryHouston Methodist HospitalHoustonUSA
  9. 9.Department of Radiation OncologyHouston Methodist HospitalHoustonUSA

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